Decellularization of porcine heart valve

Decellularization of porcine heart valves is the removal of cells along with antigenic cellular elements[1] by either physical or chemical decellularization of the tissue.[2] This decellularized valve tissue provides a scaffold with the remaining extracellular matrix (ECM) that can then be used for tissue engineering and valve replacement in humans inflicted with valvular disease.[3] Decellularized biological valves have potential benefit over conventional valves through decreased calcification which is thought to be an immuno-inflammatory response initiated by the recipient.[4]

Valvular disease

Valvular disease is caused primarily by valvular lesions stemming from infections, especially rheumatic fever (Streptococceus pyogenes), which can result in either a regurgitant or stenotic valve, or both.[5] Regurgitation results from lesions on the valve edges or annular dilation which causes backwards-flow of the blood.[5] Stenosis results in thickened leaflets due to heavy fibrosis of the valve so blood cannot flow through normally. Stenotic valves require valve replacement however conventional valves have decreased lifespan due to an inflammatory response.[6]

Tissue engineering

Xenogeneic antigens are recognized as foreign by the human body and induce an immune-mediated rejection of tissue.[3] Decellularization removes most cellular and nuclear components, and maintains the integrity of the valvular ECM, which is conserved and tolerated by transplant recipients.[3]

Physical treatments- agitation, sonication, massage, freezing and thawing are used to remove cell contents from the ECM by disrupting cell membranes. These methods are usually used in conjunction with chemical treatments in order to achieve complete decellularization.[6][7]

Chemical treatments- anionic detergent: (Sodium dodecyl sulfate (SDS)), sodium cholate, enzymatic agent (Trypsin), non-ionic detergent (Triton X-100) are all agents used to remove cells from the ECM scaffold by disrupting cellular proteins, while not affecting the mechanical strength and functional structure of the ECM through the maintenance of the collagen and elastin.[6][7] Anionic detergents cause lysis by disrupting lipid-lipid interactions. Non-ionic detergents disrupts proteins required for critical function.[6][7] Endonuclease can also be used to remove nucleic acid remnants.[7][8]

Porcine valves are used for the regeneration of biological tissue through the use of its ECM as a biological scaffold.[7][9] This tissue allows for rapid repopulation with host cells due to the cellular adhesive property of its surface.[3] Newest procedures of porcine valve decellularization include immersion decellularization[10][11] and perfusion decellularization.[11]

Benefits

Conventional mechanical valves used for replacement require anti-coagulation therapy which decreases quality of life.[4] Xenogeneic biological values require glutaraldehyde treatment to decrease the immune response to the foreign valve.[12] Still these valves eventually calcify and durability of the valve is decreased. Decellularized porcine valves are calcified to a lesser degree and may have increased mechanical strength [4] due to decreased aggregation of IgG immunoglobins in response to alpha-Gal, which is significantly increased in conventional glutaraldehyde treated biological valves.[4] Decellularized porcine valves have growth and remodeling potential as well.[4]

References
  1. Cebotari S, Tudorache I, Jaekel T, Hilfiker A, Dorfman S, Ternes W, et al. (March 2010). "Detergent decellularization of heart valves for tissue engineering: toxicological effects of residual detergents on human endothelial cells". Artificial Organs. 34 (3): 206–10. doi:10.1111/j.1525-1594.2009.00796.x. PMID 20447045.
  2. Kasimir MT, Rieder E, Seebacher G, Silberhumer G, Wolner E, Weigel G, et al. (May 2003). "Comparison of different decellularization procedures of porcine heart valves". The International Journal of Artificial Organs. 26 (5): 421–7. doi:10.1177/039139880302600508. PMID 12828309.
  3. Schenke-Layland K, Vasilevski O, Opitz F, König K, Riemann I, Halbhuber KJ, et al. (September 2003). "Impact of decellularization of xenogeneic tissue on extracellular matrix integrity for tissue engineering of heart valves". Journal of Structural Biology. 143 (3): 201–8. doi:10.1016/j.jsb.2003.08.002. PMID 14572475.
  4. Bloch O, Golde P, Dohmen PM, Posner S, Konertz W, Erdbrügger W (October 2011). "Immune response in patients receiving a bioprosthetic heart valve: lack of response with decellularized valves". Tissue Engineering. Part A. 17 (19–20): 2399–405. doi:10.1089/ten.TEA.2011.0046. PMID 21557643. S2CID 36527124.
  5. Guyton AC, Hall JE (2006). Medical Physiology (11th ed.). Pennsylvania, PHIL: Elsevier.
  6. Liao J, Joyce EM, Sacks MS (March 2008). "Effects of decellularization on the mechanical and structural properties of the porcine aortic valve leaflet". Biomaterials. 29 (8): 1065–74. doi:10.1016/j.biomaterials.2007.11.007. PMC 2253688. PMID 18096223.
  7. Patnaik SS, Wang B, Weed B, Wertheim JA, Liao J (2013-02-21). "Chapter 3: Decellularized Scaffolds: Concepts, Methodologies, and Applications in Cardiac Tissue Engineering and Whole-Organ Regeneration". =Tissue Regeneration. Frontiers in Nanobiomedical Research. 2. World Scientific. pp. 77–124. doi:10.1142/9789814494847_0003. ISBN 9789814494830. S2CID 28114835.
  8. Gallo M, Naso F, Poser H, Rossi A, Franci P, Bianco R, et al. (June 2012). "Physiological performance of a detergent decellularized heart valve implanted for 15 months in Vietnamese pigs: surgical procedure, follow-up, and explant inspection". Artificial Organs. 36 (6): E138–50. doi:10.1111/j.1525-1594.2012.01447.x. PMID 22512408.
  9. Rieder E, Seebacher G, Kasimir MT, Eichmair E, Winter B, Dekan B, et al. (May 2005). "Tissue engineering of heart valves: decellularized porcine and human valve scaffolds differ importantly in residual potential to attract monocytic cells". Circulation. 111 (21): 2792–7. doi:10.1161/CIRCULATIONAHA.104.473629. PMID 15911701.
  10. Chow JP, Simionescu DT, Warner H, Wang B, Patnaik SS, Liao J, Simionescu A (January 2013). "Mitigation of diabetes-related complications in implanted collagen and elastin scaffolds using matrix-binding polyphenol". Biomaterials. 34 (3): 685–95. doi:10.1016/j.biomaterials.2012.09.081. PMC 3496025. PMID 23103157.
  11. Sierad LN, Shaw EL, Bina A, Brazile B, Rierson N, Patnaik SS, et al. (December 2015). "Functional Heart Valve Scaffolds Obtained by Complete Decellularization of Porcine Aortic Roots in a Novel Differential Pressure Gradient Perfusion System". Tissue Engineering. Part C, Methods. 21 (12): 1284–96. doi:10.1089/ten.TEC.2015.0170. PMC 4663650. PMID 26467108.
  12. Bastian F, Stelzmüller ME, Kratochwill K, Kasimir MT, Simon P, Weigel G (April 2008). "IgG deposition and activation of the classical complement pathway involvement in the activation of human granulocytes by decellularized porcine heart valve tissue". Biomaterials. 29 (12): 1824–32. doi:10.1016/j.biomaterials.2008.01.005. PMID 18258297.
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